Cell Signaling

Receptor-Free Signaling

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Science  25 Feb 2011:
Vol. 331, Issue 6020, pp. 989
DOI: 10.1126/science.331.6020.989-a

Heterotrimeric guanine nucleotide–binding proteins (G proteins) are central regulators of many physiological processes in mammals and are thus prime targets for the development of therapeutics. In animals, G proteins are activated through an interaction with G protein–coupled receptors (GPCRs). GPCRs trigger the exchange of guanosine diphosphate for guanosine triphosphate, which activates the G protein alpha subunit and frees it from the receptor complex.

Arabidopsis thaliana plants have a G protein alpha subunit (AtGPA1) but do not have GPCRs. Instead, guanine nucleotide exchange by AtGPA1 is constitutively active. Jones et al. used x-ray crystallography, molecular dynamics simulations, and biochemical analyses to explore the structural basis for this unusual property. Their results showed the presence of a helical domain in AtGPA1 that is more disordered and dynamic than its mammalian counterpart. In mammals, the stability of interactions between the helical domain and the catalytic domain prevents nucleotide exchange; however, the plant protein has no such restriction. A mammalian G alpha protein lost its stability—and nucleotide exchange increased by over 150-fold—when the helical domain from the plant protein was swapped in. Understanding the properties of AtGPA1 may help unravel the mechanisms controlling receptor-activated G proteins in mammals.

Sci. Signal. 4, ra8 (2011).

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